Abstract

Two thiourea-based chiral solvating agents (CSAs), S-1 and S-2, were evaluated for the enantiomeric discrimination of representative α-arylacetic acids by 1H NMR spectroscopy in the presence of DMAP. Enantiomeric discrimination was assessed by monitoring chemical shift nonequivalence (ΔΔδ) arising from the formation of diastereomeric host–guest complexes. S-1 exhibited concentration-dependent enantiomeric discrimination toward all investigated carboxylic acid derivatives, reaching a maximum ΔΔδ value of 0.021 ppm. In contrast, S-2 failed to produce detectable signal splitting under identical experimental conditions. A 1D ROESY experiment together with association constant measurements supported the proposed diastereomeric host–guest complexation model and the preferential binding of one enantiomer by S-1. To further expand the substrate scope, two thiohydantoin derivatives were also examined, and S-1 produced measurable chemical shift nonequivalences, with the largest ΔΔδ value reaching 0.019 ppm. Comparison with previously reported thiourea-based CSAs further highlighted the importance of hydrogen-bonding ability, aromatic anisotropy, and overall molecular architecture in governing enantiomeric discrimination. Overall, these findings provide useful structural insights for the rational design of thiourea-based chiral solvating agents for NMR enantiomeric analysis.

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